title: Stroke-induced brain parenchymal injury drives blood-brain barrier early leakage kinetics: a combined in vivo/in vitro study.
abstract: The disappointing clinical outcomes of neuroprotectants challenge the relevance of preclinical stroke models and data in defining early cerebrovascular events as potential therapeutic targets. The kinetics of blood-brain barrier (BBB) leakage after reperfusion and the link with parenchymal lesion remain debated. By using in vivo and in vitro approaches, we conducted a kinetic analysis of BBB dysfunction during early reperfusion. After 60 minutes of middle cerebral artery occlusion followed by reperfusion times up to 24 hours in mice, a non-invasive magnetic resonance imaging method, through an original sequence of diffusion-weighted imaging, determined brain water mobility in microvascular compartments (D*) apart from parenchymal compartments (apparent diffusion coefficient). An increase in D* found at 4 hours post reperfusion concurred with the onset of both Evans blue/Dextran extravasations and in vitro BBB opening under oxygen-glucose deprivation and reoxygenation (R). The BBB leakage coincided with an emerging cell death in brain tissue as well as in activated glial cells in vitro. The co-culture of BBB endothelial and glial cells evidenced a recovery of endothelium tightness when glial cells were absent or non-injured during R. Preserving the ischemic brain parenchymal cells within 4 hours of reperfusion may improve therapeutic strategies for cerebrovascular protection against stroke.
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Kuntz
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mysiorek
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pétrault
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] IMPRT-IFR114, Lille, France [3] UDSL, Lille, France [4] CHULille, Département de Pharmacologie Médicale, EA 1046, Lille, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Pétrault
authors.affiliation: 1] Département des Microscopies, Université François Rabelais, Tours, France [2] Faculty of Bioengineering & Bioinformatics, 119991, Moscow State University, Moscow, Russia.
authors.forename: Rustem
authors.initials: R
authors.lastname: Uzbekov
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] IMPRT-IFR114, Lille, France [3] UDSL, Lille, France [4] CHULille, Département de Pharmacologie Médicale, EA 1046, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Roméo
authors.initials: R
authors.lastname: Cecchelli
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] UArtois, LBHE, EA 2465, Lens, France [3] IMPRT-IFR114, Lille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bérézowski
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D016923:Cell Death; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D005947:Glucose; D010100:Oxygen